This invention is concerned with the levorotatory enantiomers of 3-lower alkoxycyproheptadines, potent antiserotonin agents with a low order of antihistaminic activity and substantially free of any anticholinergic activity. Antiserotonin agents are useful in the prophylactic treatment of vascular headache such as migraine and cluster headaches.
Lower alkoxycyproheptadines are disclosed and generically claimed in U.S. Pat. No. 3,014,911 and 3-methoxycyproheptadine is specifically disclosed therein. However, there is no suggestion that the lower alkoxy compounds disclosed are racemic mixtures; that stable dextroand levorotatory forms could be synthesized; nor that the enantiomers thereof would have different pharmacological activities.
The racemic 3-lower alkoxy derivatives are potent antiserotonin agents with a modest degree of antihistaminic activity, but like most such agents they cause annoying side effects such as dry mouth and blurring of the vision, resulting from concomittant anticholinergic properties.
It has now been found that 3-lower alkoxycyproheptadines do exist in stable enantiomeric forms and, surprisingly, that the levorotatory enantiomers are invested with all of the antiserotonin activity found in the racemates, whereas the anticholinergic activity of the racemates resides in the dextrorotatory enantiomers. This separation of pharmacological properties is extremely important from a therapeutic viewpoint in that the undesirable anticholinergic side effects are eliminated.
Thus, it is an object of this invention to provide the levorotatory enantiomers of 3-lower alkoxycyproheptadines and pharmaceutically acceptable salts thereof, a process for their syntheses, pharmaceutical formulations thereof, and a method of producing an antiserotonin effect in a patient in need of such treatment by administration of one of the novel compounds of this invention.